tbuckley/cabot-search huggingface dataset:
337 Dupilumab treatment is not associated with an increased overall risk of infections in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis
Authors: Elaine C Siegfried, Michael J Cork, Peter D Arkwright, Andreas Wollenberg, Lawrence F Eichenfield, Michele Ramien, Faisal A Khokhar, Zhen Chen, Annie Zhang, Sonya L Cyr
Journal: British Journal of Dermatology (2023)

Abstract Patients with atopic dermatitis (AD) have an increased risk of infection, including skin infections. Previous studies in children aged 6–11 years and adolescents showed that dupilumab is not associated with an increased risk of overall infections and is associated with a lower incidence of skin infections compared with a placebo. This post-hoc analysis reports the impact of dupilumab treatment on infections, including skin infections, in children aged 6 months to 5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled trial (NCT03346434, part B), children aged 6 months to 5 years with moderate-to-severe AD (Investigator’s Global Assessment score ≥3) were randomized 1 : 1 to subcutaneous dupilumab every 4 weeks (200 mg if baseline weight was ≥5 to &amp;lt;15 kg, 300 mg if weight was ≥15 to &amp;lt;30 kg) or placebo with concomitant low-potency topical corticosteroids for 16 weeks. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) and systemic anti-infective medication use (nP/100PY) were used to compare treatment groups. 162 patients were randomized to dupilumab (n = 83) or placebo (n = 79). During the 16-week treatment period, total infections rates were numerically lower in the dupilumab-treated group (nP/100PY: 185.2) compared with the placebo-treated group (nP/100PY: 245.7). Fewer infections of skin-structure and soft tissues were reported in the dupilumab group (nP/100PY: 24.7) compared with the placebo group (nP/100PY: 40.2). Dupilumab-treated patients had significantly lower rates of non-herpetic skin infections (nP/100PY: 42.7) than placebo-treated patients (nP/100PY: 92.7; P &amp;lt; 0.05 vs. placebo). There was no significant difference in rates of herpetic skin infections between the dupilumab (nP/100PY: 20.0) and placebo groups (nP/100PY: 17.1; P = 0.817 vs. placebo). No helminthic infections were reported in either group. Systemic anti-infective medication use was significantly less frequent in the dupilumab group (nP/100PY: 104.7) compared with placebo (nP/100PY: 203.0; P &amp;lt; 0.05 vs. placebo). The overall safety of dupilumab was consistent with the known safety profile. Dupilumab treatment is associated with lower overall infections and significantly lower non-herpetic skin infections than placebo in children aged 6 months to 5 years with moderate-to-severe AD.
319 Effects of omega-3 fatty acid supplementation on atopic dermatitis
Authors: Alyssa M Abdelnour, Sarah J Shareef, Kaitlin Kreuser, Kurt Ashack
Journal: British Journal of Dermatology (2023)

Abstract Oral supplements are commonly used by patients to enhance skin health for aesthetic purposes and in response to cutaneous disorders. Currently, the Food and Drug Administration (FDA) is not authorized to approve the efficacy or safety of dietary supplements prior to public marketing. Therefore, evidence-based medicine is needed for dermatologists to better counsel patients regarding oral supplementation. Physicians must take this into consideration while treating patients with chronic conditions, such as atopic dermatitis (AD). AD is the most common cutaneous inflammatory disease affecting individuals from infancy through adulthood. Prevention and management are focused on avoiding environmental triggers, daily skin care with emollients and/or topical steroids, and decreasing systemic inflammation. Patients with AD use various treatment options and over-the-counter supplements throughout their lifetime. Interestingly, omega-3 fatty acids (O3FA) are marketed for their anti-inflammatory effects and have been widely studied to understand health benefits. To our knowledge, the effects of oral supplementation of O3FA (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) for AD are not summarized in the literature. Thus, this study was conducted to examine O3FA’s impact on AD and ultimately, to determine if supplementation is an effective therapy for the prevention and/or treatment of AD. A comprehensive electronic search with EPA and DHA for atopic dermatitis in PubMed/MEDLINE, Cochrane Central, Embase, and Google Scholar yielded 45 articles. Duplicate, non-English articles and irrelevant articles were excluded. These parameters resulted in 38 articles being excluded as they did not meet study qualifications. Therefore, seven articles are included in this review. Of the included articles, 2/7 studies discussed an improvement in skin inflammation with O3FA supplementation, while 5/7 did not find a significant difference in the prevention of allergic disease. On the other hand, one trial resulted in a significant decline in the prevalence of eczema and another indicated significant clinical improvement compared to baseline, but not in comparison to the placebo. O3FA supplementation is not effective in preventing allergic symptoms, but may decrease the prevalence of AD and provide clinical improvement. Further evaluation is needed to characterize the efficacy of O3FA supplementation in the prevention and treatment of AD.
334 Baseline demographics and family disease history in patients with atopic dermatitis: an update from the GLOBOSTAD registry
Authors: Piergiacomo Calzavara-Pinton, Jarmila Čelakovská, Hilde Lapeere, Gregor Holzer, Mona Al-Ahmad, Chia-Yu Chu, Jiangming Wu, Marius Ardeleanu, Kwinten Bosman
Journal: British Journal of Dermatology (2023)

Abstract The efficacy and safety of dupilumab have been reported previously based on data from controlled clinical trials. The GLOBOSTAD study extends the scope of these trials by providing real-world data. This analysis reports baseline demographics and family disease history in patients with atopic dermatitis (AD) who received treatment with dupilumab in a real-world setting. This 5-year, international, multicentre, non-interventional study (GLOBOSTAD; NCT03992417) included patients ≥12 years old with moderate-to-severe AD (Investigator’s Global Assessment score ≥3) who received dupilumab treatment based on country-specific prescribing criteria. Data reported are for the population at baseline (N = 952; data cut-off: March 2022) in 22 countries. In the 952 patients included at baseline, mean (standard deviation) age at AD onset was 11.1 (16.0) years. Male patients represented 57.8% of patients and White patients 65.2%. The majority of patients were enrolled from Italy (17.2%), Japan (12.4%) and Spain (11.3%). Family history of type 2 inflammatory conditions (number of patients [%]) was prevalent, including AD (364 [38.2%]), asthma (238 [25%]), allergic rhinitis (219 [23%]), food allergies (74 [7.8%]), recurrent or chronic urticaria (31 [3.3%]), nasal polyposis (21 [2.2%]), eosinophilic esophagitis (11 [1.2%]) and other atopic/allergic conditions (39 [4.1%]). Most cases of type 2 inflammatory conditions were reported in first-degree relatives. Most patients enrolled in the GLOBOSTAD study developed AD during pre-adolescence. Family history of select type 2 inflammatory conditions, including AD, asthma and allergic rhinitis, was present in a moderate proportion of patients.
288 Once-daily crisaborole as a long-term maintenance treatment in patients with mild-to-moderate atopic dermatitis: A 52-week clinical trial
Authors: Richard Gower, JinHua Xu, Maryam S Alam, John C Su, Daniela E Myers, Paul Sanders, Bonnie Vlahos, Chuanbo Zang, Jar Lan, John  Werth
Journal: British Journal of Dermatology (2023)

Abstract Treatments for atopic dermatitis (AD) often fail to achieve lasting disease control despite patient adherence, with safety concerns limiting the long-term use of many therapies. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. Crisaborole has the potential as a long-term maintenance therapy. To assess the long-term efficacy and safety of crisaborole once daily as a maintenance treatment to reduce the incidence of flares in patients who had achieved response with treatment with crisaborole twice daily. CrisADe CONTROL (NCT04040192) was a randomized, double-blind, vehicle-controlled, 52-week, phase 3 study of patients aged ≥ 3 months with mild-to-moderate AD involving ≥ 5% treatable body surface area. In an open-label run-in period, patients received crisaborole twice daily for up to 8 weeks. Patients who achieved success per Investigator’s Static Global Assessment (ISGA; ISGA score of 0 [clear] or 1 [almost clear] with a ≥ 2-grade improvement from baseline) and ≥ 50% reduction from baseline on the Eczema Area and Severity Index during the run-in were randomly assigned to receive blinded crisaborole or vehicle once daily during the 52-week maintenance period. Patients who experienced a flare (ISGA score ≥2) during the maintenance period switched to crisaborole twice daily for up to 12 weeks (assessed every 4 weeks); if the flare resolved (ISGA score ≤ 1), patients resumed their blinded once-daily treatment. Endpoints included flare-free maintenance until the onset of the first flare (primary), the number of days without flare and the number of flares. The incidence of treatment-emergent adverse events was also evaluated. Of 270 randomly assigned patients, 135 were assigned to crisaborole and 135 to a vehicle once daily. The median time of flare-free maintenance was longer for patients treated with crisaborole vs. vehicle (111 vs. 30 days, respectively; P = 0.0034). The mean number of flare-free days was higher for patients treated with crisaborole vs. vehicle (234.0 vs. 199.4, respectively; P = 0.0346). The mean number of flares was lower for patients treated with crisaborole vs. vehicle (0.95 vs. 1.36, respectively; P = 0.0042). Crisaborole was well tolerated, with no unexpected safety findings or new safety signals when used as a maintenance treatment for 52 weeks. Once-daily treatment with crisaborole was effective and well tolerated for long-term maintenance treatment and flare reduction in adult and paediatric patients with mild-to-moderate AD.
313 Assessment of racial differences of atopic dermatitis characteristics in a diverse outpatient cohort in the United States
Authors: Eric Sanfilippo, Sneha Iyer, Nisha Patel, Jonathan I Silverberg
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis (AD) can present differently across racial groups. To promote equality and consistency, dermatologists and other providers should properly recognize the heterogeneous manifestations of AD across racial groups. Yet, little is known about differences in how the commonly different features of AD occur by race. We assessed racial differences in the proportions of select key features of AD. The healthcare claims database from a large metropolitan tertiary care medical centre was queried for patients with physician-diagnosed AD using International Classification of Disease, Tenth Revision and Clinical Modification codes L20.x. Medical records were reviewed for demographics, comorbidities and documentation of Hanifin-Rajka criteria. The frequency of each criterion was evaluated by race (White, Black, Asian and Multiracial–Other). Overall, 766 patients with AD were included in the study; 374 (48.8%) were White, 284 (37.1%) Black, 89 (11.6%) Asian and 19 (2.5%) multiracial/other, 558 (68.2%) were female, 50 (6.1%) were age &amp;lt;18 years, 456 (55.7%) age 18–49 years and 313 (38.2%) age ≥50 years. Compared to White patients, Black patients had significantly higher proportions of personal (81.4% vs. 57.3%) and family (63.3% vs. 42.2%) history of atopic disease, perifollicular accentuation (60.6% vs. 36.9%) and xerosis on physical exam (84.2% vs. 73.9%)(P ≤ 0.03 for all). Multiracial/other patients had elevated proportions of a history of dry skin (81.3%), xerosis on physical exam (86.7%) and elevated Immunoglobulin E levels (75.0%). Black and multiracial/other patients had food hypersensitivity compared to White patients (50.0% and 71.4% vs. 35.1%, P = 0.04). There were marginally significant differences in the proportion of early-age AD onset (56.9% vs. 41.8%, P = 0.07) and anterior neck fold involvement (42.6% vs. 25.3%, P = 0.06) in Asian compared to White patients. There were no significant racial differences in the likelihood of other Hanifin-Rajka criteria, including pruritus, flexural dermatitis, chronic dermatitis, ichthyosis, nipple eczema, hand/foot dermatitis, immediate skin reactivity, subcapsular cataracts, cutaneous infections, pruritus when sweating, intolerance to wool/lipid solvents, environmental/emotional factors worsening AD, or white dermatographism. Our results suggest there are racial differences in AD characteristics even within a single region. These differences may be attributable to population-differences in genetics, environmental exposures, skincare practices etc. Future research is needed to understand the mechanisms and treatment responses of these heterogeneous AD presentations.
314 Injection site reactions from an integrated analysis of phase 2 and phase 3 clinical trials of lebrikizumab treatment in moderate-to-severe atopic dermatitis
Authors: Melinda Gooderham, Vivian Y Shi, Andreas Wollenberg, Jacob P Thyssen, Tiago Torres, Esther Garcia Gil, Laia Bardolet, Chitra R Natalie, Amber R Atwater, Fangyi Zhao, Andrew Blauvelt
Journal: British Journal of Dermatology (2023)

Abstract Lebrikizumab is an injectable, IgG4 monoclonal antibody that selectively binds to interleukin-13 with high affinity. Injection-site reactions (ISRs) are localized adverse events in the immediate site of administration of a drug and are common with injectable therapies. This analysis reports ISRs in patients from eight lebrikizumab (LEB) clinical trials in atopic dermatitis. To report ISRs in patients with moderate-to-severe atopic dermatitis treated with LEB, from an integrated safety analysis of phase 2 and 3 LEB clinical trials. These data sets include adolescents and adult patients who received at least one dose of LEB from a total of eight atopic dermatitis clinical trials, including four 16-week placebo-controlled clinical trials. Eight trials consist of: ADvocate1, ADvocate2, ADhere, ADore, ADjoin (ongoing), ARBAN, TREBLE and Phase 2b study. Treatment duration ranged from a single dose to 100 weeks. ISRs were defined using the preferred terms from the Medical Dictionary for Regulatory Activities high-level term, injection site reactions, excluding terms related to joints. This analysis includes ISRs frequencies in patients treated with LEB compared to placebo (ALL PC week 0–16), and all patients who received any dose of LEB (ALL LEB), and reports ISRs type, exposure adjusted incidence rates (EAIR) per 100 patient-years, the timing of ISRs occurrence, and ISRs leading to discontinuation. In the ALL PC week 0–16 analysis, 2.6% (n = 20/783, EAIR 9.0) of patients in the LEB group reported ISRs vs. 1.5% (n = 6/404 EAIR 5.4) in the placebo group. Injection site pain (n = 7, 0.9%) and injection site erythema (n = 7, 0.9%) were the most frequent reactions reported in the LEB group. Most ISRs were mild or moderate, with only 1 (0.1%) severe event. In the ALL LEB analysis, 3.1% of patients reported ISRs (n = 53/1720, EAIR 3.3). Injection site pain (n = 16, 0.9%) and injection site erythema (n = 12, 0.7%) were the most frequent reactions. Almost all reports were mild or moderate, with 3 (0.2%) severe. The incidence of ISRs did not increase with a longer duration of LEB exposure. The majority of ISRs were reported between weeks 0 and 16 (n = 38, 2.2%). The frequency of ISRs from week 16 to 32 was 1.0% (n = 15), from week 32 to 48 was 0.4% (n = 4) and from week 48 to 64 was 0.2% (n = 2). Treatment discontinuation due to ISRs occurred in a few patients (n = 5, 0.3%). Overall, a low proportion of patients reported ISRs (&amp;lt;3%) with a numerically higher frequency of LEB-treated patients who reported ISRs compared to placebo (1.5%). Most events were mild or moderate in severity, did not lead to treatment discontinuation, occurred within the first 16 weeks of treatment, and ISRs incidence did not increase with a longer duration of exposure.
322 Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized, double-blinded, placebo-controlled phase 3 trials (ADvocate1 and ADvocate2)
Authors: Andrew Blauvelt, Jacob P Thyssen, Emma  Guttman-Yassky, Thomas Bieber, Jose Manuel Carrascosa, Eric Simpson, David  Rosmarin, Hany Elmaraghy, Eric Meskimen, Chitra R Natalie, Zhuqing Liu, Chenjia Xu, Evangeline Pierce, MaryAnn Morgan-Cox, Jonathan I Silverberg
Journal: British Journal of Dermatology (2023)

Abstract Lebrikizumab (LEB) is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13. To evaluate the efficacy and safety of LEB monotherapy in patients with moderate-to-severe atopic dermatitis (AD) in two identical phase 3 trials ADvocate1 (ADv1) and ADvocate2 (ADv2). Patients who responded to LEB 250 mg every 2 weeks (LEB Q2W) at the end of the 16-week induction period were re-randomized in a 2 : 2 : 1 ratio to receive LEB Q2W, LEB 250 mg every 4 weeks (LEB Q4W) or placebo (LEB withdrawal) for an additional 36 weeks. Response, at week 16, was defined as achieving an IGA (0, 1) with a ≥2-point improvement or EASI75 and no use of rescue medication. Efficacy outcomes reported at week 52 included IGA (0, 1), EASI 75, ≥4-point reduction in Pruritis Numeric Rating Scale (NRS), EASI 90 and DLQI ≥4-point. Safety analysis was conducted on all patients who received ≥1 dose of LEB. Patients maintained IGA (0, 1) in LEB Q2W (ADv1, 75.8%; ADv2, 64.6%), LEB Q4W (ADv1, 74.2%; ADv2, 80.6%) and LEB withdrawal (ADv1, 46.5%; ADv2, 49.8%). Maintenance of EASI75 was, in LEB Q2W (ADv1, 79.2%; ADv2, 77.4%), LEB Q4W (ADv1, 79.2%; ADv2, 84.7%) and LEB withdrawal (ADv1, 61.3%; ADv2, 72.0%). For Pruritus NRS ≥4-point improvement from baseline, patients-maintained improvement in the LEB Q2W (ADv1, 81.2%; ADv2, 90.3%), LEB Q4W (ADv1, 80.4%; ADv2, 88.1%) and LEB withdrawal (ADv1, 65.4%; ADv2, 67.6%). Maintenance of EASI90 was, in LEB Q2W (ADv1, 66.1%; ADv2, 61.5%), LEB Q4W (ADv1, 66.6%; ADv2, 67.4%) and LEB withdrawal (ADv1, 45.5%; ADv2, 36.9%). DLQI ≥4-point improvement from baseline was LEB Q2W (ADv1, 64.0%; ADv2, 59.0%), LEB Q4W (ADv1, 62.7%; ADv2, 73.0%) and LEB withdrawal (ADv1, 57.7%; ADv2, 45.5%). TEAEs were reported by 58.1% (ADv1) and 67.8% (ADv2) LEB-treated patients at week 52. Serious adverse events were reported by 3.3% of ADv1 patients and 2.7% of ADv2 patients. In ADv1 and ADv2, 2.3% and 3.9% of patients reported an adverse event leading to treatment discontinuation, respectively. Both LEB Q2W and LEB Q4W maintained improvement in all reported outcomes for the treatment of moderate-to-severe AD through 52 weeks. The safety profile was consistent with previously published data.
321 Cancer risk with topical pimecrolimus and tacrolimus for atopic dermatitis: systematic review and Bayesian meta-analysis
Authors: Alexandro W L Chu, Niveditha Devasenapathy, Melanie Wong, Archita Srivastava, Renata Ceccacci, Clement Lin, Margaret MacDonald, Aaron Wen, Jeremy Steen, Mitchell Levine, Lonnie Pyne, Julie Wang, Jonathan M Spergel, Jonathan I Silverberg, Peck Y Ong, Monica O’Brien, Stephan A Martin, Peter A Lio, Mary Laura Lind, Jennifer LeBovidge, Elaine Kim, Joey Huynh, Matthew Greenhawt, Winfred T Frazier, Lina Chen, Anna De Benedetto, Mark Boguniewicz, Rachel N Asiniwasis, Lynda Schneider, Derek K Chu
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis affects millions worldwide and is effectively managed by topical treatments, including topical calcineurin inhibitors, pimecrolimus and tacrolimus. In 2005 and 2011, the FDA released reviews associating topical calcineurin inhibitors with a theoretical cancer risk, albeit an uncertain association. We systematically reviewed the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors. We systematically identified randomized controlled trials, comparative, and non-comparative non-randomized studies from database inception to 6 June 2022, from MEDLINE, EMBASE, GREAT, LILACS, ICTRP, FDA, EMA, company registers and relevant citations. We included studies in any language addressing the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors for greater than 3 weeks. We excluded split-body studies. We conducted a Bayesian meta-analysis and used the GRADE approach to determine the certainty of the evidence. A multidisciplinary panel including patients, advocacy groups and care providers, set an a priori threshold of 1 in 1000 risk difference as a clinically important effect. We analysed 121 studies (52 randomized controlled trials and 69 non-randomized studies) including 3.4 million patents followed for a mean of 11 months (range: 0.7–120). The absolute risk of any cancer with topical calcineurin inhibitor exposure was neither different from controls (absolute risk 4.70 per 1000 with topical calcineurin inhibitor exposure vs. 4.56 per 1000 without; odds ratio 1.03 [95% credible interval 0.94–1.11], moderate-certainty evidence) nor the general US population (4.6 per 1000). Findings were similar in infants, children, and adults, and were robust to trial sequential, subgroup and sensitivity analyses. Among infants, children and adults with atopic dermatitis, moderate-certainty evidence shows that topical calcineurin inhibitors do not increase the risk of cancer. These findings support the safe use of topical calcineurin inhibitors in the management of patients with atopic dermatitis. Our findings provide actional information to inform updated clinical practice guidelines, product labels and continuing education for care providers, to clarify the safe usage of topical calcineurin inhibitors.